DESCRIPTION Oligodendrocytes are recognized by myelin gene expression and complex process formation. The final shape of oligodendrocytes is thought to be determined by intrinsic growth strategies, since even in the absence of neurons, oligodendrocytes will form processes reminiscent of their in vivo counterparts. The thin processes of oligodendrocytes display robust motility. This motility enables oligodendrocytes to interact with axons and commence myelination. While the molecular basis of oligodendroglial thin process motility is not known, motility in other cell types has been demonstrated to be a function of actin remodeling. Gelsolin, an actin-binding protein which regulates actin network formation, mediates cellular movement in fibroblasts. The expression of gelsolin in oligodendrocytes suggests a role for gelsolin in oligodendroglial thin process motility. If gelsolin regulates thin process growth in oligodendrocytes, the changes in gelsolin activity will cause changes in oligodendroglial shape and size. To test this hypothesis, the following three specific aims are proposed. First, the effect of gelsolin anti-sense treatment on process formation will be investigated. Second, the effect of decreased gelsolin activity on myelin gene expression will be ascertained. Finally, changes in gelsolin activity by astrocytes will be documented. Successful completion of this project will provide documentation of gelsolin's role in oligodendroglial process formation. Since process formation must be stimulated to trigger remyelination in the adult brain, the control of process formation is an important consideration in the treatment of human demyelinative disorders. Regulation of actin motility by gelsolin in the thin processes of oligodendrocytes may be the means to stimulate process formation and re-myelination in the adult brain.